In our continuing investigation of mechanisms of interferon production and its role in host defense against viruses, we are now studying interferon production in human herpesvirus infections, particularly in relationship to immune responses. The role of cell-mediated immunity in these infections is of particular interest, as it is commonly defective in individuals with underlying disease who fail to handle these viruses well, either on a congenital (thymus deficiency) or acquired basis (Hodgkin's disease, immunosuppressive therapy, etc.). In vitro assays are being devised for interferon and other mediator substances (lymphotoxin, migration inhibitory factor, etc.) as immune specific products of lymphocytes in response to viral antigens. The course of such responses in relationship to single and recurrent infections will be studied as will be their role in recovery in normal and compromised hosts. Special attention will be paid to correlation of the level of cell-mediated immunity and local interferon production in the viral target organs to determine what role sensitized lymphoid cells might play at the site of infection. The influence of several therapeutic modalities on disease course and these responses will be determined, including nucleoside analogues, interferon, specific antibody and transfer factor.